Project 1 is a continuation of investigations on the occurrence of the spectrum of neurodegenerative diseases that are highly prevalent on Guam. It has yet to be determined whether neurodegenerative diseases occur in this population as a consequence of a single exposure or are explained by a multi-factorial model, such as genetic predisposition with environmental modifiers. There has been a remarkable shift in the disease manifestations over the past 4 decades. This shift has been from predominantly amyotrophic lateral sclerosis (ALS) in the 1950s to predominantly Parkinson-dementia complex (PDC) and pure dementia (D) in the 1970-1980s. The incidence of ALS appeared to peak in the late 1950s and as a distinct disease has gradually declined during each subsequent decade. A similar pattern of decline for PDC which peaked in the mid to late 1960s has also been reported although other studies indicate that the rate may not have changed. Mean age of onset for both ALS and PDC have shown a 10 to 15 year increase over the past four decades. A recent comprehensive study has confirmed that, regardless of clinical manifestation, age, male gender, and living in the southern villages of Guam and on Rota continue to be risk factors for developing either ALS or PDC. The proposed investigation consists of two parts. One is a follow-up study of two previously well established cohorts with the target diseases. In this part the scientific goals are to determine if familial clustering of ALS/PDC is still prevalent and whether or not the incidence of ALS/PDC is continuing to decrease. In the second part, a casecontrols study, the hypothesis will be tested that consumption of native food, specifically fadang, is a risk factor related to the development of ALS/PDC. The results of these efforts may provide a basis for establishing a potential Biologic explanation for this unique occurrence of neurodegenerative diseases and may ultimately lead to specific intervention and preventive strategies. This will directly benefit the people of Guam who have suffered from this terrible burden for so long, and would provide a model for studying other age-related neurodegenerative disorders such as Alzheimer disease.